Authors: | Dyck, J. A.; Maul, G. G.; Miller, W. H. Jr; Chen, J. D.; Kakizuka, A.; Evans, R. M. |
Article Title: | A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein |
Abstract: | Acute promyelocytic leukemia (APL) is associated with a t(15; 17) translocation that creates the promyelocyte-retinoic acid receptor α (PML-RARα) fusion gene. Immunohistochemistry demonstrates that PML is a part of a novel macromolecular organelle (including at least three other nuclear proteins) referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted into a microparticulate pattern as a consequence of the expression of the PML-RAR oncoprotein. RA treatment of APL cells triggers a reorganization of PML to generate normal-appearing PODs. We propose that PML-RAR is a dominant negative oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel structure, but it can be ascribed an imputed function such that its disruption leads to altered myeloid maturation; this may represent a novel oncogenic target. © 1994. |
Keywords: | immunohistochemistry; oncoprotein; human cell; nonhuman; animal cell; gene expression; protein assembly; neoplasm proteins; animalia; transcription factors; nuclear proteins; oncogenes; leukemia, promyelocytic, acute; fluorescent antibody technique; leukemogenesis; tumor suppressor proteins; promyelocytic leukemia; translocation, genetic; cell nucleus; cell organelle; macromolecule; macromolecular substances; chromosomes, human, pair 17; chromosomes, human, pair 15; tretinoin; receptors, retinoic acid; humans; human; priority journal; article; retinoic acid binding protein |
Journal Title: | Cell |
Volume: | 76 |
Issue: | 2 |
ISSN: | 0092-8674 |
Publisher: | Cell Press |
Date Published: | 1994-01-28 |
Start Page: | 333 |
End Page: | 343 |
Language: | English |
DOI: | 10.1016/0092-8674(94)90340-9 |
PROVIDER: | scopus |
PUBMED: | 8293467 |
DOI/URL: | |
Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |